Research
Work Hard, Be Kind!
Work Hard, Be Kind!
We have uncovered a role for insulin signaling and the forkhead transcription factor (Foxo) in regulating diapause in Cx. pipiens. Although we are gaining a clearer picture of the hormonal pathways underlying diapause in Cx. pipiens, the molecular regulation of proliferating fat body cells and its role on the extended lifespan of diapausing mosquitoes are not well understood. Recent studies have begun to show that H3K27me2 loss is closely related to the processes of carbohydrate energy metabolism and aging. It also shows that this H3K27me2 loss is linked to the Insulin/Foxo signaling, suggesting that H3K27me2 loss likely to regulate the downstream genes relevant to diapause traits including fat storage and consumption, stress tolerance, and extended lifespan. The precise mechanism of how H3K27me2 induces or suppresses genetic targets, and the subsequent control of diapause traits in Cx. pipiens, will be crucial to our understanding of dormancy in other disease vectors. Furthermore, since the histone remodeling by H3K27 methylation is utilized by flies and nematodes for their coordinated developmental control, we anticipate that our proposed work will have a broad impact that extends beyond mosquito populations, providing insights for the regulation and prevention of various arthropod-borne diseases.
# Major focuses of current research include:
1. To establish the link between diapause-relevant genes and the chromatin distribution of H3K27me2 in fat body tissues.
2. To identify and characterize the genes that are activated by H3K27me2 modification to generate the overwintering fat storage and consumption.
3. To define the roles of the histone demethylase (UTX) and the histone methyltransferases (E(z) and ESC) in regulating H3K27me2 in order to understand the mechanisms that extend the lifespan of diapausing mosquitoes.
Photoperiod, or daylength, is a reliable seasonal predictor that most temperate organisms can measure, but precisely how they do this is unclear. Insect diapause is a physiologically dynamic state of arrested development that is similar to mammalian hibernation in that both diapausing insects and hibernating mammals interpret the short days of late summer and early fall as a harbinger of winter’s arrival. Researchers have long known that short days cause females of the Northern house mosquito, Culex pipiens, and other insects that overwinter as adults, to divert physiological resources from reproduction towards survival, and that this is caused by low levels of Juvenile Hormone. More recently, we have uncovered a role for insulin signaling and the forkhead transcription factor (FOXO) in regulating diapause in Cx. pipiens. Although we are gaining a clearer picture of the hormonal pathways underlying diapause in Cx. pipiens, we still do not know how any animal is able to measure and interpret daylength. Accordingly, there is a critical need to determine how animals translate environmental signals into molecular regulators so that we can fully understand how mosquitoes and other animals properly time their growth and reproduction to coincide with favorable environmental conditions, and alter their physiology to survive harsh season.
# Major focuses of current research include:
1. Determine how altering the clock affects seasonal responses.
2. Identify genetic targets of clock genes that regulate diapause-relevant hormonal and signaling pathways.
3. Uncover how seasonal phenotypes are generated in wild type and clock-null mosquitoes.
The blacklegged tick, Ixodes scapularis, is the principal vector of Borrelia burgdorferi, the causative agent of Lyme disease in North America. A key feature of tick ecology is the ability to enter diapause—a developmental arrest that synchronizes life stages with seasonal environmental changes and enables overwintering survival. Diapause not only ensures tick population persistence but also provides a temporal refuge for pathogens, facilitating year-to-year maintenance of B. burgdorferi in natural transmission cycles. Despite its importance, the molecular mechanisms that couple diapause regulation with pathogen persistence remain poorly defined. In particular, the role of circadian clock pathways—central regulators of environmental timekeeping—in shaping diapause biology and pathogen interactions is unknown.
This project seeks to uncover the molecular and physiological mechanisms that link diapause regulation in I. scapularis with the capacity to harbor and transmit B. burgdorferi. Specifically, we will: (1) characterize the expression and functional roles of genes implicated in diapause and circadian clock regulation using qRT-PCR, RNA interference, and protein assays; (2) investigate how diapause alters physiological states that may influence pathogen persistence under controlled environmental conditions; and (3) identify molecular interactions between diapause- and circadian-related pathways that integrate environmental cues with seasonal pathogen maintenance. By directly examining how diapause regulation intersects with pathogen biology, this research will generate fundamental insights into the seasonal ecology of Lyme disease vectors. The findings are expected to advance understanding of how molecular timing systems in ticks sustain B. burgdorferi populations through adverse seasons, thereby shaping disease transmission risk. Ultimately, this work may highlight novel molecular targets for disrupting pathogen persistence in tick vectors and reducing the public health burden of Lyme disease.